Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
  • A61K9/7023—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
  • A61K9/703—Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K8/00—Cosmetics or similar toiletry preparations
  • A61K8/02—Cosmetics or similar toiletry preparations characterised by special physical form
  • A61K8/0208—Tissues; Wipes; Patches
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K9/00—Medicinal preparations characterised by special physical form
  • A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q1/00—Make-up preparations; Body powders; Preparations for removing make-up
  • A61Q1/12—Face or body powders for grooming, adorning or absorbing
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q19/00—Preparations for care of the skin
  • A61Q19/10—Washing or bathing preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
  • A61Q17/005—Antimicrobial preparations
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
  • A61Q5/00—Preparations for care of the hair
  • A61Q5/02—Preparations for cleaning the hair
• • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
  • Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
  • Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
  • Y10T428/00—Stock material or miscellaneous articles
  • Y10T428/31504—Composite [nonstructural laminate]
  • Y10T428/31855—Of addition polymer from unsaturated monomers
  • Y10T428/31909—Next to second addition polymer from unsaturated monomers
  • Y10T428/31913—Monoolefin polymer

Definitions

• This invention relates to a safe, economical delivery system for cosmetics, toiletries, and over-the-counter) drugs. More particularly, it relates to a pouch-like delivery system having a tricot-like film covering which assists in evenly and safely distributing topical medicaments.
• Nonwoven fabrics have been used for a wide variety of applications for at least fifty years.
• Nonwoven fabrics are textile-like materials produced directly from a web of fibers so as to eliminate the many time consuming steps involved in converting staple length fibers into woven or knitted goods.
• Nonwoven fabrics are inherently porous structures, i.e. they contain openings or pores allowing for the passage of fluids such as air and water or aqueous solutions.
• nonwoven fabrics may be tailored so as to have good softness, drapability, and tactile impression. Due to their desirable characteristics, nonwovens have been employed as facing materials for absorbent products such as disposable diapers, washcloths and the like.
• an apertured plastic film may be produced by placing a heated thermoplastic sheet material on a patterned perforated surface and applying a vacuum thereto. The vacuum pulls the softened sheet material through the perforations, thereby causing the film to rupture and form apertures.
• U.S. 3,929,135 (Thompson et al.) describes perforated topsheet materials for absorbent devices such as sanitary napkins, incontinent pads, bandages and the like. These topsheet materials are constructed from liquid impervious materials such as low density polyethylene and comprise a plurality of tapered capillaries each of which has a base opening in the plane of the top sheet and an apex opening which is remote from the plane of the top sheet.
• U.S. 3,929,135 (Thompson et al.) describes perforated topsheet materials for absorbent devices such as sanitary napkins, incontinent pads, bandages and the like. These topsheet materials are constructed from liquid impervious materials such as low density polyethylene and comprise a plurality of tapered capillaries each of which has a base opening in the plane of the top sheet and an apex opening which is remote from the plane of the top sheet.
• 4,324,276 (Mullane) describes an apertured formed film having a caliper of less than about 0.030 inch (0.075 cm), an open area of a least 35% and a plurality of apertures at least 75% of which have an equivalent hydraulic diameter (EHD) of at least 0.025 inch (0.064 cm) , which is useful as a topsheet for disposable absorbent products of the type mentioned above.
• EHD equivalent hydraulic diameter
• U.S. 4,839,216 (Curro et al.) describes a debossed and perforated plastic material produced by providing a starting film on a perforated forming surface and applying an unconstrained liquid stream to the upper surface of the starting film.
• European Patent Application 0 304 617 (Kao Corporation) describes a covering sheet for a sanitary article.
• the covering sheet comprises an opaque, hydrophobic film having land portions and recesses, said recesses being formed to have a bottom portion and side walls.
• the side walls have a slanting part which is provided with an opening such that the slanting part is not covered by the land portion.
• U.S. 4,690,679 describes an apertured film comprising a first layer of a first polymeric film and a second layer of a second polymeric film.
• This patent states that apertured films wherein the apertures have average equivalent circular diameters ranging from about 0.010 inches (0.0254 cm) to about 0.030 inches (0.0762 cm) are useful as covering materials for absorbent products.
• the fabric as previously defined is a tricot-like fabric made from LLDPE, LDPE, PP, EVA, EMA (ethylene methyl acrylate) and coextrusion or blend of above-identified polymers, blown or cast film with 0.5 to 3 mil thickness.
• U.S. Patent 5,368,581 (Smith et.al.) describes a method of applying two or more drug agents to skin from a single dispensing applicator system having a plurality of applicator pads. It consists of a C-fold or face-to-face shield which must be separated by hand by tearing the facings (C-folds). The liquids are impregnated onto the pads prior to tearing and mixed in-situ on the skin by rubbing.
• U.S. Patent 5,368,581 Smith et.al.
• Patent 3,647,305 (Baket et.al.) describes a similar applicator with C-fold or face-to-face sealing which is convertible to a multi-finger pad with drug agents.
• the drug agents are applied from either a saturated porous nonwoven pad or open-celled foam.
• the basic pad is a non-sealable latex film in which the non-sealable latex film is coated with a heat sealable latex film.
• the basic pad must be opened or inverted prior to use in or to apply the contents.
• U.S. 2,621,784 (Boytham) describes a medicant applicator package consisting of the following: a single sheet of impervious fusible material with face-to-face sealing of the absorbent medicant containing pads in a manner to form a G-fold. It also contains a compartment for placement of hand or fingers on the back. The impervious material must be removed prior to using a string which surrounds the entire package. All of the above suffer from one or more of deleterious drawbacks. For example, the package of Smith et al. has many applicator pads which are C-folded (face-to-face).
• products may cause entrapment of the active ingredient, i.e., the inability to expel the full dosage of active ingredient from the pad.
• all of the above products and, in particular, the applicator pad require that the active ingredient be impregnated into absorbent materials such as non-woven or sponge.
• Tricot knit fabrics are durable, soft and drapable.
• the tricot fabric structure provides high quality perception, good aesthetics, and luxurious appeal.
• No apertured film in the market today has tricot appearance and feel.
• Another object of this invention is to provide a delivery system for medicaments which is simple to use, expels a large percentage of medicament upon finger pressure and yet is neat, protecting the skin of the individual who is making the application of medicament.
• Figure 1 depicts a cross-section of one embodiment of a delivery system pouch according to this invention.
• Figure 2 depicts a cutaway plan view of the top of the pouch of Figure 1.
• Figure 3 depicts a plan view of the bottom of a delivery system pouch according to this invention.
• Figure 4 depicts a plan view of another embodiment of a delivery system pouch according to this inveniton.
• Figure 5 depicts culture tubes inoculated with samples taken from female Harley Guinea Pigs as set forth in Example 10 below. summa y of the Invention
• This invention relates to an improved package system for delivery of drugs, cosmetics and toiletries which are intended for topical use. These can be used on humans, animals and plants.
• any products which can be dispensed using such a package system can be incorporated in the improved package system of this invention so as to deliver a composition to an inanimate object or surface.
• the improved package system of this invention may be used to deliver shoe polish to a shoe surface, keeping the hands clean while eprforming this task.
• the products of this invention relate to a delivery pouch having a backing, a delivery facing and a coating of active material therebetween.
• the delivery pouch preferably is made of novel apertured films which comprise a plurality of micro-holes defined by a network of fiber-like elements or microstrips of drawn plastic as described in copending patent application United States Serial No. 08/307,973.
• This film fabric which is tricot-like, is applicable to personal care and drug products as unique delivery systems as a result of the inherent properties as defined herein.
• other films or fabrics having similar attributes may be used as well. This represents numerous advantages to the consumer as will become apparent hereinafter.
• the products of this invention preferably contain at least an impermeable backing, a coating of medicament and, overlying said coating and sealed to said impermeable backing. More preferably they contain the following elements:
• the products of this invention provide many benefits over the systems described heretofore.
• the bonding between the detachable cover and the deliver facing is weaker than that between the delivery facing and the impervious backing,thereby permitting the detachable cover to be peeled back without loosening the delivery facing from the backing.
• the detachable cover is preferably a polymer film, preferably a polyalkylene film such as polypropylene, polyethylene, polyester or paraffin wax- coated paper.
• the peel tab is preferably a polypropylene and ethylene-vinyl acetate coextruded film or paper/film with adhesive coating.
• the ethylene-vinyl acetate side of the coextruded film can be sealed to the polypropylene detachable cover material and create a strong seal which can readily assist in removing the detachable cover from the delivery facing without affecting the ability of the delivery facing to be adhered to the impervious backing.
• the delivery facing is preferably a soft, two- dimensional film with a three-dimensional structure having a fabric-like feel.
• the film itself is two-dimensional, but it is made in such a way that the final product has three dimensions, i.e.. it has undulations.
• the film does not have interstitial spaces, which would permit the active ingredient to be entrapped therein.
• the film or fabric useful in the products of this invention preferably has a three dimensional structure containing small fibrils and highly apertured areas. It delivers good aesthetics, fabric feel, and efficient fluid transport, is clean and dry in use, is extremely soft, and lint-free.
• the delivery facing has three dimensional containment and wiping functionality. This is most advantageous for a drug product where control of dosage for safety and efficacy are important.
• the delivery facing should contain tube-like holes, which substantially eliminate the previously defined problem of entrapment. By simple finger pressure, the contents are relatively easily dispensed to the part of the body or substrate requiring the drug. Convenience of use together with softness, less messy, excellent control of dosage offer a significant improvement over the prior art.
• the delivery facing is made from "APEX"-type film products, as set forth in U.S. Patent Application Serial No. 07/744,744, which is hereby incorporated herein by reference.
• the delivery facing is a tricot- type APEX film having from about 5 to about 10% open area.
• This film is very soft and fabric-like, has maximum active ingredient containment before use and minimum residue entrapment after use. Theoretically, each open area serves as a small tube. The amount of application can be controlled by the pressure applied.
• the APEX fabric/film and process render versatility in design and delivery of the product onto hair and skin. Depending upon the nature of the active ingredient and its formulation, the number, size and position of the apertures in the surface of the film may be altered. The three dimensional nature and fibril/space structure allows the product to be easily charged into the fabric.
• the delivery facing is preferably made of a perforated or reticulated polyethylene or polyethylene/ethylene vinyl acetate film or a light ⁇ weight hydrophobic nonwoven fabric made from: polyethylene/polyethylene terephthalate or a polyethylene/polypropylene (bicomponent fiber, such as BICO available from BASF), polyethylene or polypropylene spunbonded, polypropylene fiber. It can also be a RETICULON * film as described in U.S. Patents Nos. 4,690,679 and 4,710,186, which are hereby incorporated herein by reference.
• Apertures in the films of the delivery facing of this invention can have an equivalent circular diameter (ECD) of from about 2 to about 25 mils, more preferably from about 2 to about 7 mils. It can have from about 100 to about 10,000 apertures per square inch. Preferably, it should be from about 5 to about 20 mils in thickness, more preferably from about 10 to about 20 mils, most preferably from about 13 to about 15 mils.
• the active ingredient is preferably contained in a viscous gel, cream or ointment formulation in order for maximum drug delivery control. The viscosity of the active ingredient formulation should be from about 10,000 to about 10,000,000 cPs.
• the delivery facing has larger apertures, it can accommodate a delivery of a formulation of higher viscosity if the facing has smaller apertures, it can accommodate the delivery of a formulation of very low viscosity such as an oil.
• a formulation of very low viscosity such as an oil.
• Those of ordinary skill in the art can adjust the viscosity of the active ingredient formulation, depending upon the aperture-size of the delivery facing, or vice versa. Components of acceptable gels, creams or ointments are well-known to those of ordinary skill.
• the pouch products of this invention contain a finger grab on the exterior of the impermeable backing.
• This finger grab can be an additional facing which is folded and sealed to the impermeable facing on three sides, leaving a fourth area free to accommodate a finger or fingers.
• This finger grab facilitates wiping and delivery of the dermatological product to the substrate. It also prevents the pouch from slipping and flapping around.
• the finger grab is preferably a polyolefin film, such as polyethylene, polyethylene/ ethylene vinyl acetate coextruded film, or polypropylene/ethylene vinyl acaetate coextruded film.
• Pouch product 10 contains the following elements. Impervious backing 20 is coated with an active ingredient formulation coating 30 in paste or gel form. Adjacent coating 30 is delivery facing 40, having a coating-facing side and an outward-facing side. Delivery facing 40 is sealed to impervious backing 20 around their perimeters. Adjacent the outward-facing side of delivery facing 40 is detachable cover 50, which has a delivery facing side and an outward-facing side. Delivery facing 40 is sealed to detachable cover 50 around their perimeters.
• detachable cover 50 has an anterior end 55 and a posterior end 57. At the anterior end 55, detachable cover 50 optionally contains a peel tab 60, which is shorter than the length of the detachable cover from anterior end 55 to posterior end 57. Peel tab 60 is preferably sealed to detachable cover 50 only at the anterior end 55 of the detachable cover 50.
• the seal strength between peel tab 60 and detachable cover 50 is preferably greater than that between detachable cover 50 and delivery facing 40, so as to permit the peel tab 60 to remove detachable cover 50 from delivery facing 40 without removing detachable cover 50 from impervious backing 20 as well.
• the products of this invention contain a finger pocket 70 on the outward-facing side of impervious backing 20.
• Finger pocket 70 is preferably shorter than impervious backing 20 and is preferably sealed to impervious backing 20 around its perimeter, but for one loose portion 75.
• Finger pocket 70 is preferably large enough to accommodate at least one of the user' s fingers.
• Figure 2 depicts a cutaway view of the top of product 10, wherein peel tab 60 is affixed to detachable cover 50 along line 65. The construction of the product can be seen clearly, as coating 30 is applied to impermeable backing 20. Delivery facing 40 overlies cotaing 30 as well as impermeable backing 20.
• the products of this invention contain a peel tab composed of polypropylene coextruded with ethylene vinyl acetate; a detachable cover made from polypropylene, wherein the detachable cover is sealed to the polypropylene side of the peel tab; and the remaining layers made up of polyethylene or a coextruded film of polyethylene and ethylene vinyl acetate.
• delivery facing and impermeable backing are sealed such that the polyethylene sides are sealed together.
• the pouch products of this invention may be rectangular, square, round or oval in shape or any shape that is within the skill of one of ordinary skill in the art.
• the system is particularly advantageous where drug delivery to abraded skin such as diaper rash, wounds or the like represents a potential problem with cross- infection, particularly from HIV virus or the like. It can be designed for multiple use and/or one-use and is disposable, as the system is environmentally acceptable.
• Active ingredients which can be dispensed using the products of this invention include, but are not limited to: antimicrobials, deodorants, antiperspirants, skin and hair care products, retinoids, vaginal products. facial acne products, rectal cleansers, anti-itch powders, diaper rash, hair and body cleansers, conditioners, wound cleansers, and any others known to those of ordinary skill in the art.
• the products of this invention are particularly well- suited for the application of antifungal products to the skin.
• This format is particularly attractive because the therapeutic agent is aliquotted, and neatly packaged to minimize finger contact with the lesion as well as with the agent.
• fungal/yeast infections are often found in moist intertriginous regions, such the inguinal, under-breast, and axillary areas, as well as the foot. Many patients find treating these areas with a bare finger offensive and would prefer using an inert support.
• the pouch format is particularly attractive since the drug used is already aliquotted and the patient has an immediate, contained and clean tool for application.
• an antimycotic such as Spectazole cream (1% econazole nitrate) is particularly well-suited for this type of application.
• a perforation line for making APEX film is equipped with a driven unwind, a drum with a forming surface, three manifolds, a drying section, and a winder.
• the manifolds provide constrained liquid steam as an energy source.
• the forming surface contains a plurality of openings extending through the thickness of the drum. - 15 -
• each opening There are two sizes of openings staggered in rows (the rows being oriented in the cross-direction) along the machine direction.
• the space between sets of one row of larger openings and one row of smaller openings is greater than the space between one row of larger and one row of smaller openings within the set.
• the top portion of each opening has a conical shape.
• the conical shaped surfaces are relatively smooth with varying undulations.
• a film material was made using Exxon Chemical EMB-631. polyethylene, having a thickness of 0.8 mil. The material was run at a rate of 50 yards per minute (ypm) . The manifolds were held at a pressure of 1350 pounds per square inch (psi). The water temperature was 160°F water. The resulting film had an open area of about 10%, an average hole size of ECD 5 mil and a hole size ECD variation coefficient of 58%. The Frazier air value of the film was 350 cfm.
• a film material was made using Exxon Chemical EMB-631 polyethylene, having a thickness of 0.80 mil. The material was run at a rate of 50 yards per minute (ypm) . The manifolds were held at a pressure of 1000 pounds per square inch (psi). The water temperature was 160°F water. The resulting film had an open area of about 3%, an average hole size of ECD 3 mil and a hole size ECD variation coefficient of 54%. The Frazier air value of the film was 200 cfm. The film contained approximately 3,400 holes per square inch. - 16 - Example 3
• a film material was made using Exxon Chemical EMB-631 polyethylene, having a thickness of 0.95 mil. The material was run at 50 yards per minute (YPM). The manifolds were held at a pressure of 1350 pounds per square inch (psi). The water temperture was 160F. The resulting film had an open area of about 5%, an average hole size of ECD 3 mil and a holes ECD variation coefficient of 73%.
• the Frazier air value of the film was 288 cfm.
• the film contained approximately 4,790 holes per square inch.
• the pouches had four layers constructed as follows:
• the bottom sheet was made of Exxon polyethylene film EMB-633, having a thickness of 1.25 mil. Over this layer was applied zinc oxide ointment in the amount of 2 grams (g).
• Apex tricot film made in accordance with the process set forth in Example 2, made of EMB-631 polyethylene film, having a thickness of 13 mil, an open area of 3%, a hole size of 3 mils was then applied over the zinc oxide ointment to the backing film of polyethylene, sleeve side up.
• the ointment was coated onto the backsheet with a coater knife (Pacific Scientific) set at 1 full turn pass zero and at 22.0.
• the ointment was coated over a window cut into a MYLAR (available from E. I. duPont de Nemours of Wilmington, Delaware) thermoplastic material.
• a detachable facing layer composed of Exxon EMB-631 polyethylene film having a thickness of about 0.8 mil was then applied to the delivery facing layer using heat.
• the materials were assembled and placed onto a Jenkins press, heat-sealed and die cut using 80 psi air pressure, 265°F temperature.
• the seal strength between the delivery facing and the impervious backing sheet was greater than that between the delivery facing and the detachable cover due to the difference in the material used in the product.
• An antimicrobial product containing 2% chlorohexadine gluconate, amine oxide, fragrance, thickener and fragrance are prepared and incorporated into a pouch product in accordance with Example 4. are prepared in the same manner.
• Talc and fragrance were incorporated into the pouch in accordance with the method set forth in Example 4.
• the pouch application of talc and fragrance in accordance with the teachings of this invention produced less dust or fines upon use compared to conventional packaging.
• a standard gel shampoo system of 20% sodium lauryl (3) ether sulfate, 3% lauric diethanolamide, thickener, preservative dyes and fragrance in a water base are prepared.
• the gel shampoo system is incorporated into a pouch product in accordance with the method set forth in Example 4.
• the product dispenses easily and foams copiously on hair and/or skin.
• vaginal lubricant such as K-Y* Jelly is incorporated into the products of this invention in accordance with Example 4.
• the pouch products of this invention can be readily inserted and wiped across the vagina in order to dispense vaginal lubricant and/or a spermicide formulation internally without occasioning excess material on the fingers.
• Trichophyton mentagrophytes #9201 was grown on Sabouraud' s dextrose agar (SDA) in Roux bottles for 14- 15 days at 32 C. Fungal spores were removed with a small volume of Tween-saline and the suspension was poured into a graduated cylinder. The mixture was diluted 1:1 with honey and homogenized in a blender. The suspension was then filtered through a funnel lined with a sterile gauze pad.
• SDA Sabouraud' s dextrose agar
• Nembutal Female Harley guinea pigs, 350-450 g, were obtained from Charles River Laboratories. Each animal was weighed and the anesthetized with an injection of Nembutal
• DTM Dermatophyte test medium
• the pouch contained two grams of total reagent; preliminary experiments demonstrated that 50% of the total reagent was expressed from the pouch by vigorous wiping.
• Results are set forth in Table 1 below and in Figure 5. It can be seen from examining the Table and Figures that at the initiation of the experiment, at least seven of the animals in each group cultured positive for fungi. After one week of treatment, eight of the untreated animals cultured positive but none of the treated animals. At the end of two weeks, six of the untreated animals continued to demonstrate viable fungus but the two treated groups were again negative. At the end of - 21 - three weeks, the data show that the infection burned itself out (a characteristic of this animal), but it is significant that infection did not reappear in the treated groups. Thus, the application of an antimycotic using the pouch products of this invention is at least as effective as the conventional applicator method and demonstrates that it is effective as a method of delivery antifungal agents.

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• Health & Medical Sciences (AREA)
• Life Sciences & Earth Sciences (AREA)
• Animal Behavior & Ethology (AREA)
• General Health & Medical Sciences (AREA)
• Public Health (AREA)
• Veterinary Medicine (AREA)
• Engineering & Computer Science (AREA)
• Bioinformatics & Cheminformatics (AREA)
• Epidemiology (AREA)
• Dermatology (AREA)
• Chemical & Material Sciences (AREA)
• Medicinal Chemistry (AREA)
• Pharmacology & Pharmacy (AREA)
• Birds (AREA)
• Biomedical Technology (AREA)
• Cosmetics (AREA)
• Medicinal Preparation (AREA)
• Orthopedics, Nursing, And Contraception (AREA)

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• 1995
  • 1995-06-08 US US08/495,727 patent/US6156323A/en not_active Expired - Lifetime
• 1996
  • 1996-05-30 IN IN984CA1996 patent/IN188446B/en unknown
  • 1996-06-05 AU AU60463/96A patent/AU6046396A/en not_active Abandoned
  • 1996-06-05 WO PCT/US1996/008979 patent/WO1996041623A2/en active Application Filing
  • 1996-06-07 KR KR1019960020191A patent/KR100567143B1/ko not_active Expired - Fee Related
  • 1996-06-07 ZA ZA9604873A patent/ZA964873B/xx unknown
  • 1996-07-08 TW TW085108212A patent/TW359613B/zh not_active IP Right Cessation

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